Endothelial cell properties are affected by hemodynamics, various systemic chemicals and signals, and their attachment matrix. In an effort to extend current understanding of both atherogenesis and factors complicating successful treatment of occluded coronary arteries, this project will investigate the effects of hemodynamic forces, angiotensin I/II, and the cellular inflammatory response on endothelial cell physiology. Local synthesis of angiotensin II by endothelial membrane bound angiotensin converting enzyme (ACE) and the angiotensin type I receptor (AT1) may have potent effects on local endothelial dysfunction and the development of coronary artery disease. The inflammatory cytokine interleukin-l (IL-1) likely plays an important role in the alteration of endothelial phenotype observed in the presence of cellular stressors such as extremes of hydrodynamic pressure and angiotensin I/II. Many effects of IL-1 upon vascular endothelial cells are identical to those associated with angiotensin exposure and vascular activation by fluid forces. As such, work will be performed to elucidate the contributions of IL-1 to the effects of culture stimulation with pressure and angiotensin. Syndecans-l (present in the glycocalyx) and 4 (co-localized to focal adhesions) are common endothelial cell surface molecules that can be readily shed in response to cellular injury or stress and thereby promote monocyte adhesion. We hypothesize that modulation of two in vitro endothelial cell culture properties 1) hemodynamic pressure and 2) angiotensin I/II concentrations affects endothelial cell phenotype as related to 1) glycocalyx properties, 2) receptor/protein expression, and 3) attachment characteristics. Encompassed by this hypothesis are the mechanisms by which pressure and angiotensin I/II exert their effects. It is proposed that pressure and angiotensin I/II activate cell stress signaling pathways (i.e. mitogen activated protein kinase cascades and protein kinase C) that result in the shedding of specific glycocalyx components (e.g. syndecan proteoglycans) and the induction of proinflammatory physiological responses (e.g. interleukin-1 production, monocyte adhesion receptor production, monocyte chemoattractant protein-1production). It is further proposed that while pressure and angiotensin directly induce these events, the production of intlerleukin-1 significantly amplifies each of the physiological responses and becomes a controlling factor upon endothelial dysfunction.